Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Dentistry - Biomaterials, Philips van Leydenlaan 25, 6525EX Nijmegen, the Netherlands; School of Stomatology, Shandong University, Jinan, Shandong, People's Republic of China.
Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Dentistry - Biomaterials, Philips van Leydenlaan 25, 6525EX Nijmegen, the Netherlands.
J Control Release. 2020 Aug 10;324:134-145. doi: 10.1016/j.jconrel.2020.05.004. Epub 2020 May 5.
In periodontal treatment, patient differences in disease phenotype and treatment responses are well documented. Therefore, therapy duration and dosage should be tailored to the requirements of individual patients. To facilitate such personalized medication, a tunable and controllable system is needed to deliver drugs directly into the diseased periodontal pockets. The current study established a system to achieve different drug release rates and periods by incorporating bioactive agents into poly(lactic-co-glycolic acid) (PLGA) microspheres dispersed into a novel thermo-reversible polyisocyanopeptide (PIC) hydrogel. Specifically, two drugs, i.e. doxycycline and lipoxin, were separately loaded into acid-terminated and ester-capped PLGA by electrospraying. Different formulations were developed by loading the two kinds of PLGA microspheres with different mass ratios in the PIC gels. The results demonstrated that the PIC-PLGA vehicle exhibited appropriate injectability, long-term structural stability, and no obvious in vivo inflammatory response for the desired clinical application. Furthermore, the release profiles of drugs could be manipulated by adjusting the loaded mass ratio of acid- and ester- terminated PLGA microspheres in the PIC gels. The more ester-capped PLGA was used, the slower the release rate and the longer the release period, and vice versa. Additionally, the released drugs still preserved their bio-efficacy. This PIC-PLGA system can be further developed and tested in translational studies to demonstrate the final clinical benefit.
在牙周病治疗中，患者的疾病表型和治疗反应差异已得到充分证实。因此，治疗持续时间和剂量应根据患者的具体需求进行调整。为了实现这种个性化治疗，需要开发一种可调可控的系统，以便将药物直接输送到患病的牙周袋中。本研究通过将生物活性剂掺入聚（丙交酯-乙交酯）（PLGA）微球中，并将其分散到新型热可逆聚异氰酸酯肽（PIC）水凝胶中，建立了一种实现不同药物释放率和释放周期的系统。具体来说，两种药物，即强力霉素和脂氧素，分别通过电喷法装载到酸端基和酯封端的 PLGA 中。通过在 PIC 凝胶中以不同的质量比装载这两种 PLGA 微球，开发了不同的配方。结果表明，PIC-PLGA 载体具有适当的可注射性、长期的结构稳定性和无明显的体内炎症反应，适用于预期的临床应用。此外，通过调整 PIC 凝胶中酸端基和酯端基 PLGA 微球的载药质量比，可以控制药物的释放曲线。使用的酯封端 PLGA 越多，释放速度越慢，释放周期越长，反之亦然。此外，释放的药物仍保持其生物疗效。该 PIC-PLGA 系统可以进一步开发和测试，以证明其最终的临床益处。
